tbuckley/cabot-search huggingface dataset:
ERS technical standard: Global Lung Function Initiative reference values for exhaled nitric oxide fraction (<i>F</i><sub>ENO<sub>50</sub></sub>)
Authors: Marieann Högman, Cole Bowerman, Luis Chavez, Holger Dressel, Andrei Malinovschi, Thomas Radtke, Sanja Stanojevic, Irene Steenbruggen, Steve Turner, Anh Tuan Dinh-Xuan
Journal: European Respiratory Journal (2023)

Background Elevated exhaled nitric oxide fraction at a flow rate of 50 mL·s −1 ( F ENO 50 ) is an important indicator of T-helper 2-driven airway inflammation and may aid clinicians in the diagnosis and monitoring of asthma. This study aimed to derive Global Lung Function Initiative reference equations and the upper limit of normal for F ENO 50 . Methods Available individual F ENO 50 data were collated and harmonised using consensus-derived variables and definitions. Data collected from individuals who met the harmonised definition of “healthy” were analysed using the generalised additive models of location, scale and shape (GAMLSS) technique. Results Data were retrospectively collated from 34 782 individuals from 34 sites in 15 countries, of whom 8022 met the definition of healthy (19 sites, 11 countries). Overall, height, age and sex only explained 12% of the between-subject variability of F ENO 50 (R 2 =0.12). F ENO device was neccessary as a predictor of F ENO 50 , such that the healthy range of values and the upper limit of normal varied depending on which device was used. The range of F ENO 50 values observed in healthy individuals was also very wide, and the heterogeneity was partially explained by the device used. When analysing a subset of data in which F ENO 50 was measured using the same device and a stricter definition of health (n=1027), between-site heterogeneity remained. Conclusion Available F ENO 50 data collected from different sites using different protocols and devices were too variable to develop a single all-age reference equation. Further standardisation of F ENO devices and measurement are required before population reference values might be derived.
Mortality surrogates in combined pulmonary fibrosis and emphysema
Authors: An Zhao, Eyjolfur Gudmundsson, Nesrin Mogulkoc, Coline van Moorsel, Tamera J. Corte, Pardeep Vasudev, Chiara Romei, Robert Chapman, Tim J.M. Wallis, Emma Denneny, Tinne Goos, Recep Savas, Asia Ahmed, Christopher J. Brereton, Hendrik W. van Es, Helen Jo, Annalisa De Liperi, Mark Duncan, Katarina Pontoppidan, Laurens J. De Sadeleer, Frouke van Beek, Joseph Barnett, Gary Cross, Alex Procter, Marcel Veltkamp, Peter Hopkins, Yuben Moodley, Alessandro Taliani, Magali Taylor, Stijn Verleden, Laura Tavanti, Marie Vermant, Arjun Nair, Iain Stewart, Sam M. Janes, Alexandra L. Young, David Barber, Daniel C. Alexander, Joanna C. Porter, Athol U. Wells, Mark G. Jones, Wim A. Wuyts, Joseph Jacob
Journal: European Respiratory Journal (2023)

Idiopathic pulmonary fibrosis (IPF) with coexistent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts.
Cost Savings and Waste Reduction Through Redispensing Unused Oral Anticancer Drugs
Authors: Elisabeth M. Smale, Bart J. F. van den Bemt, Eibert R. Heerdink, Ingrid M. E. Desar, Toine C. G. Egberts, Charlotte L. Bekker, Anneloes de Bruin, Bas van Vlijmen, Desirée Burger, Thijs Balk
Journal: JAMA Oncology (2023)

New strategies targeting waste are required to improve financial and ecologic sustainability of expensive therapies, such as oral anticancer drugs, that frequently remain unused by patients. Redispensing unused oral anticancer drugs seems to be a promising strategy when drug quality is guaranteed.
Mortality in ST-Segment Elevation Myocardial Infarction With Nonobstructive Coronary Arteries and Mimickers
Authors: Odayme Quesada, Mehmet Yildiz, Timothy D. Henry, Seth Bergstedt, Jenny Chambers, Ananya Shah, Larissa Stanberry, Lucas Volpenhein, Dalia Aziz, Rebekah Lantz, Cassady Palmer, Justin Ugwu, Muhammad J. Ahsan, Ross F. Garberich, Heather S. Rohm, Frank V. Aguirre, Santiago Garcia, Scott W. Sharkey
Journal: JAMA Network Open (2023)

Importance The clinical characteristics and prognosis of patients with ST-segment elevation myocardial infarction (STEMI) with nonobstructive coronaries (MINOCA) are largely unknown. Objective To assess differences in 5-year mortality in patients presenting with STEMI due to MINOCA and MINOCA mimickers as compared with obstructive disease. Design, Setting, and Participants A retrospective analysis of a prospective registry-based cohort study of consecutive STEMI activations at 3 regional Midwest STEMI programs. STEMI without a culprit artery and elevated troponin levels were categorized as MINOCA (absence of coronary artery stenosis &amp;amp;gt;50% and confirmed or suspected coronary artery plaque disruption, epicardial coronary spasm, or coronary embolism/thrombosis) or MINOCA mimickers (takotsubo cardiomyopathy, myocarditis, or nonischemic cardiomyopathy). Data were analyzed from March 2003 to December 2020. Main Outcomes and Measures Adjusted Cox regression analysis was used to assess 5-year mortality risk in STEMI presenting with MINOCA and MINOCA mimickers in comparison with obstructive disease. Results Among 8560 consecutive patients with STEMI, mean (SD) age was 62 (14) years, 30% were female (2609 participants), and 94% were non-Hispanic White (4358 participants). The cohort included 8151 patients with STEMI due to obstructive disease (95.2%), 120 patients with MINOCA (1.4%), and 289 patients with MINOCA mimickers (3.8%). Patients were followed up for a median (IQR) of 7.1 (3.6-10.7) years. Patients with MINOCA and MINOCA mimickers were less likely to be discharged with cardiac medications compared with obstructive disease. At 5-year follow-up, mortality in STEMI presenting with obstructive disease (1228 participants [16%]) was similar to MINOCA (20 participants [18%]; χ 2 1 = 1.1; log-rank P = .29) and MINOCA mimickers (52 participants [18%]; χ 2 1 = 2.3; log-rank P = .13). In adjusted Cox regression analysis compared with obstructive disease, the 5-year mortality hazard risk was 1.93 times higher in MINOCA (95% CI, 1.06-3.53) and similar in MINOCA mimickers (HR, 1.08; 95% CI, 0.79-1.49). Conclusions and Relevance In this large multicenter cohort study of consecutive clinical patients with STEMI, presenting with MINOCA was associated with a higher risk of mortality than obstructive disease; the risk of mortality was similar in patients with MINOCA mimickers and obstructive disease. Further investigation is necessary to understand the pathophysiologic mechanisms involved in this high-risk STEMI population.
Nivolumab for Patients With High-Risk Oral Leukoplakia
Authors: Glenn J. Hanna, Alessandro Villa, Shuvro P. Nandi, Ruichao Shi, Anne ONeill, Mofei Liu, Charles T. Quinn, Nathaniel S. Treister, Herve Y. Sroussi, Piamkamon Vacharotayangul, Laura A. Goguen, Donald J. Annino, Eleni M. Rettig, Vickie Y. Jo, Kristine S. Wong, Patrick Lizotte, Cloud P. Paweletz, Ravindra Uppaluri, Robert I. Haddad, Ezra E. W. Cohen, Ludmil B. Alexandrov, William N. William, Scott M. Lippman, Sook-bin Woo
Journal: JAMA Oncology (2023)

Proliferative verrucous leukoplakia (PVL) is an aggressive oral precancerous disease characterized by a high risk of transformation to invasive oral squamous cell carcinoma (OSCC), and no therapies have been shown to affect its natural history. A recent study of the PVL immune landscape revealed a cytotoxic T-cell-rich microenvironment, providing strong rationale to investigate immune checkpoint therapy.
Cost-Effectiveness of Liquid Biopsy for Colorectal Cancer Screening in Patients Who Are Unscreened
Authors: Zainab Aziz, Sophie Wagner, Alice Agyekum, Yoanna S. Pumpalova, Matthew Prest, Francesca Lim, Sheila Rustgi, Fay Kastrinos, William M. Grady, Chin Hur
Journal: JAMA Network Open (2023)

Importance Despite recommendations for universal screening, adherence to colorectal cancer screening in the US is approximately 60%. Liquid biopsy tests are in development for cancer early detection, but it is unclear whether they are cost-effective for colorectal cancer screening. Objective To estimate the cost-effectiveness of liquid biopsy for colorectal cancer screening in the US. Design, Setting, and Participants In this economic evaluation, a Markov model was developed to compare no screening and 5 colorectal cancer screening strategies: colonoscopy, liquid biopsy, liquid biopsy following nonadherence to colonoscopy, stool DNA, and fecal immunochemical test. Adherence to first-line screening with colonoscopy, stool DNA, or fecal immunochemical test was assumed to be 60.6%, and adherence for liquid biopsy was assumed to be 100%. For colonoscopy, stool DNA, and fecal immunochemical test, patients who did not adhere to testing were not offered other screening. In colonoscopy–liquid biopsy hybrid, liquid biopsy was second-line screening for those who deferred colonoscopy. Scenario analyses were performed to include the possibility of polyp detection for liquid biopsy. Exposures No screening, colonoscopy, fecal immunochemical test, stool DNA, liquid biopsy, and colonoscopy–liquid biopsy hybrid screening. Main Outcomes and Measures Model outcomes included life expectancy, total cost, and incremental cost-effectiveness ratios. A strategy was considered cost-effective if it had an incremental cost-effectiveness ratio less than the US willingness-to-pay threshold of $100 000 per life-year gained. Results This study used a simulated cohort of patients aged 45 years with average risk of colorectal cancer. In the base case, colonoscopy was the preferred, or cost-effective, strategy with an incremental cost-effectiveness ratio of $28 071 per life-year gained. Colonoscopy–liquid biopsy hybrid had the greatest gain in life-years gained but had an incremental cost-effectiveness ratio of $377 538. Colonoscopy–liquid biopsy hybrid had a greater gain in life-years if liquid biopsy could detect polyps but remained too costly. Conclusions and Relevance In this economic evaluation of liquid biopsy for colorectal cancer screening, colonoscopy was a cost-effective strategy for colorectal cancer screening in the general population, and the inclusion of liquid biopsy as a first- or second-line screening strategy was not cost-effective at its current cost and screening performance. Liquid biopsy tests for colorectal cancer screening may become cost-effective if their cost is substantially lowered.
Cost-Effectiveness of Blood-Based Biomarkers for Colorectal Cancer Screening—An Ounce of Prevention Is Worth a Pound of Cure
Authors: John M. Inadomi
Journal: JAMA Network Open (2023)

Zainab Aziz, BS; Sophie Wagner, BS; Alice Agyekum, BS; Yoanna S. Pumpalova, MD; Matthew Prest, MS; Francesca Lim, MS; Sheila Rustgi, MD; Fay Kastrinos, MD, MPH; William M. Grady, MD; Chin Hur, MD, MPH
Multi-omic screening of invasive GBM cells reveals targetable transsulfuration pathway alterations
Authors: Joseph H. Garcia, Erin A. Akins, Saket Jain, Kayla J. Wolf, Jason Zhang, Nikita Choudhary, Meeki Lad, Poojan Shukla, Jennifer Rios, Kyounghee Seo, Sabraj A. Gill, William H. Carson, Luis R. Carette, Allison C. Zheng, David R. Raleigh, Sanjay Kumar, Manish K. Aghi
Journal: Journal of Clinical Investigation (2023)

While the poor prognosis of glioblastoma arises from the invasion of a subset of tumor cells, little is known of the metabolic alterations within these cells that fuel invasion. We integrated spatially addressable hydrogel biomaterial platforms, patient site-directed biopsies, and multi-omics analyses to define metabolic drivers of invasive glioblastoma cells. Metabolomics and lipidomics revealed elevations in the redox buffers cystathionine, hexosylceramides, and glucosyl ceramides in the invasive front of both hydrogel-cultured tumors and patient site-directed biopsies, with immunofluorescence indicating elevated reactive oxygen species (ROS) markers in invasive cells. Transcriptomics confirmed upregulation of ROS-producing and response genes at the invasive front in both hydrogel models and patient tumors. Amongst oncologic ROS, H2O2 specifically promoted glioblastoma invasion in 3D hydrogel spheroid cultures. A CRISPR metabolic gene screen revealed cystathionine gamma-lyase (CTH), which converts cystathionine to the non-essential amino acid cysteine in the transsulfuration pathway, to be essential for glioblastoma invasion. Correspondingly, supplementing CTH knockdown cells with exogenous cysteine rescued invasion. Pharmacologic CTH inhibition suppressed glioblastoma invasion, while CTH knockdown slowed glioblastoma invasion in vivo. Our studies highlight the importance of ROS metabolism in invasive glioblastoma cells and support further exploration of the transsulfuration pathway as a mechanistic and therapeutic target.
Reversible phosphorylation of a lectin-receptor-like kinase controls xylem immunity
Authors: Ran Wang, Chenying Li, Zhiyi Jia, Yaxing Su, Yingfei Ai, Qinghong Li, Xijie Guo, Zeng Tao, Fucheng Lin, Yan Liang
Journal: Cell Host & Microbe (2023)
A longitudinal single-cell atlas of treatment response in pediatric AML
Authors: Sander Lambo, Diane L. Trinh, Rhonda E. Ries, Dan Jin, Audi Setiadi, Michelle Ng, Veronique G. Leblanc, Michael R. Loken, Lisa E. Brodersen, Fangyan Dai, Laura M. Pardo, Xiaotu Ma, Suzanne M. Vercauteren, Soheil Meshinchi, Marco A. Marra
Journal: Cancer Cell (2023)

Pediatric acute myeloid leukemia (pAML) is characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains understudied in pediatric patients. We used single-cell RNA sequencing and single-cell ATAC sequencing to profile 28 patients representing different pAML subtypes at diagnosis, remission and relapse. At diagnosis, cellular composition differed between genetic subgroups. Upon relapse, cellular hierarchies transitioned toward a more primitive state regardless of subtype. Primitive cells in the relapsed tumor were distinct compared to cells at diagnosis, with under-representation of myeloid transcriptional programs and over-representation of other lineage programs. In some patients, this was accompanied by the appearance of a B-lymphoid-like hierarchy. Our data thus reveal the emergence of apparent subtype-specific plasticity upon treatment and inform on potentially targetable processes.
Inhalable Textile Microplastic Fibers Impair Airway Epithelial Differentiation
Authors: Shanshan Song, Fransien van Dijk, Gwenda F. Vasse, Qiongliang Liu, Irene F. Gosselink, Ellen Weltjens, Alex H. V. Remels, Marina H. de Jager, Sophie Bos, Chenxi Li, Tobias Stoeger, Markus Rehberg, David Kutschke, Gail W. A. van Eck, Xinhui Wu, Suzanne H. Willems, Devin H. A. Boom, Ingeborg M. Kooter, Diana Spierings, René Wardenaar, Matthew Cole, Martijn C. Nawijn, Anna Salvati, Reinoud Gosens, Barbro N. Melgert
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Microplastics are a pressing global concern and inhalation of microplastic fibers has been associated with interstitial and bronchial inflammation in flock workers. However, how microplastic fibers affect the lungs is unknown. Objectives: Our aim was to assess the effects of 12x31 µm nylon 6,6 (nylon) and 15x52 µm polyethylene terephthalate (polyester) textile microplastic fibers on lung epithelial growth and differentiation. Methods: We used human and murine alveolar and airway-type organoids as well as air-liquid interface cultures derived from primary lung epithelial progenitor cells and incubated these with either nylon or polyester fibers or nylon leachate. In addition, mice received one dose of nylon fibers or nylon leachate and 7 days later organoid-forming capacity of isolated epithelial cells was investigated. Measurements and Main Results: We observed that nylon microfibers, more than polyester, inhibited developing airway organoids and not established ones. This effect was mediated by components leaching from nylon. Epithelial cells isolated from mice exposed to nylon fibers or leachate, also formed fewer airway organoids, suggesting long-lasting effects of nylon components on epithelial cells. Part of these effects were recapitulated in human air-liquid interface cultures. Transcriptome analysis revealed upregulation of Hoxa5 post-exposure to nylon fibers. Inhibiting Hoxa5 during nylon exposure restored airway organoid formation, confirming Hoxa5's pivotal role in the effects of nylon. Conclusions: These results suggest that components leaching from nylon 6,6 may especially harm developing airways and/or airways undergoing repair and we strongly encourage to characterize both hazard of and exposure to microplastic fibers in more detail.
The difference in all-cause mortality between COVID-19 patients treated with standard of care plus placebo and those treated with standard of care alone: a network meta-analysis of randomised controlled trials of immunomodulatory kinase inhibitors
Authors: Ping-Tao Tseng, Bing-Syuan Zeng, Chih-Wei Hsu, Trevor Thompson, Brendon Stubbs, Po-Ren Hsueh, Kuan-Pin Su, Yen-Wen Chen, Tien-Yu Chen, Yi-Cheng Wu, Pao-Yen Lin, Andre F Carvalho, Dian-Jeng Li, Ta-Chuan Yeh, Cheuk-Kwan Sun, Yu-Shian Cheng, Yow-Ling Shiue, Chih-Sung Liang, Yu-Kang Tu
Journal: Journal of the Royal Society of Medicine (2023)

The aim of this network meta-analysis (NMA) was to assess whether participants assigned to a placebo and standard of care (SoC) group had different major coronavirus disease 2019 (COVID-19)-related outcomes than those assigned to SoC alone.
Chronic graft-versus-host disease detected by tissue-specific cell-free DNA methylation biomarkers
Authors: Batia Avni, Daniel Neiman, Elior Shaked, Ofer Gal-Rosenberg, Sigal Grisariu, Mona Kuzli, Ilai Avni, Andrea Fracchia, Polina Stepensky, Tsila Zuckerman, Ahinoam Lev-Sagie, Ilana Fox-Fisher, Sheina Piyanzin, Joshua Moss, Seth J. Salpeter, Benjamin Glaser, Ruth Shemer, Yuval Dor
Journal: Journal of Clinical Investigation (2023)

BACKGROUND. Accurate detection of graft versus host disease (GVHD) is a major challenge in the management of patients that undergo hematopoietic stem cell transplantation (HCT). Here we demonstrate the use of circulating cell-free DNA (cfDNA) for detection of tissue turnover and chronic GVHD (cGVHD) in specific organs.
Ann Robinson’s research reviews—16 November 2023
Authors: Ann Robinson
Journal: BMJ (2023)

Take it without a pinch of saltReducing salt intake is as effective for lowering blood pressure as commonly used first line antihypertensive drugs in people aged 50-75 years.This small, but important, study of 213 people included roughly equal numbers of people with normal blood pressure, treated blood pressure, inadequately treated blood pressure, and untreated high blood pressure.The researchers found an average lowering of 8 mm Hg in systolic blood pressure in those who reduced their usual salt intake compared with those who increased it over one week.
Reply to: Candidacy for ECMO Should Start with Ventilatory Support Optimization
Authors: Darya Rudym, Tài Pham, Craig R Rackley, Giacomo Grasselli, Matthieu Schmidt, Daniel Brodie
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to: Candidacy for ECMO Should Start with Ventilatory Support Optimization." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
TV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studies
Authors: Kristen K. Pierce, Anna P. Durbin, Mary-Claire R. Walsh, Marya Carmolli, Beulah P. Sabundayo, Dorothy M. Dickson, Sean A. Diehl, Stephen S. Whitehead, Beth D. Kirkpatrick
Journal: Journal of Clinical Investigation (2023)

BACKGROUND. Disease due to dengue viruses is a growing global health threat, causing 100-400 million cases annually. An ideal dengue vaccine should demonstrate durable protection against all four serotypes in phase 3 efficacy trials, however the lack of circulating serotypes may lead to incomplete efficacy data. Controlled human infection models help down select vaccine candidates and supply critical data to supplement efficacy trials. We evaluated the efficacy of a leading live attenuated tetravalent dengue vaccine candidate, TV005, against infection with a newly established dengue serotype 3 or an established serotype 2 challenge virus.
Effects of Positive End-Expiratory Pressure on Artery Coronary Flow in Patients with Acute Respiratory Distress Syndrome
Authors: Yoann Zerbib, Rosalie Schoux, Jack Richecoeur, Thomas Bradier, Clément Brault, Loay Kontar, Alexis Lambour, Julien Maizel, Michel Slama
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Effects of Positive End-Expiratory Pressure on Artery Coronary Flow in Patients With Acute Respiratory Distress Syndrome." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Fungal Fog in Viral Storms: Necessity for Rigor in Aspergillosis Diagnosis and Research
Authors: Simon Feys, Martin Hoenigl, Jean-Pierre Gangneux, Paul E. Verweij, Joost Wauters
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Fungal Fog in Viral Storms: Necessity for Rigor in Aspergillosis Diagnosis and Research." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Trends in the Prevalence of Chronic Obstructive Pulmonary Disease Among Adults Aged ≥18 Years — United States, 2011–2021
Authors: Yong Liu, Susan A. Carlson, Kathleen B. Watson, Fang Xu, Kurt J. Greenlund
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States. Overall COPD prevalence declined during 1999-2011. Trends in COPD prevalence during the previous decade have not been reported. CDC analyzed 2011-2021 Behavioral Risk Factor Surveillance System data to assess trends and differences in self-reported physician-diagnosed COPD prevalence among U.S. adults aged ≥18 years. Age-standardized prevalence of COPD did not change significantly from 2011 (6.1%) to 2021 (6.0%). Prevalence was stable for most states and subgroups; however, it decreased significantly among adults aged 18-44 years (average annual percent change [AAPC] = -2.0%) and increased significantly among those aged ≥75 years (AAPC = 1.3%), those living in micropolitan counties (0.8%), and among current (1.5%) or former (1.2%) smokers. COPD prevalence remained elevated in the following groups: women, adults aged ≥65 years, those with a lower education level, unable to work, living in rural areas, and who ever smoked. Evidence-based strategies, especially those tailored for adults disproportionately affected, can reduce COPD prevalence, and address the continued need for prevention, early diagnosis, treatment, and management.